Cell adhesion and morphogenesis are crucial events in craniofacial development, and errors can result in congenital anomalies. Related biological processes are being implicated in tissue repair, tumor invasion and metastasis, and AIDS pathogenesis. We are characterizing the functions of certain key proteins that we hypothesize help to regulate cytoskeletal and signaling processes essential for development, malignancy, or AIDS. The mechanisms of salivary gland morphogenesis are under investigation, with particular focus on cell-surface interactions and signal transduction. The roles of the tumor suppressor PTEN are being characterized in the regulation of cell migration and signal transduction. Roles of HIV Tat and other molecules in regulating HIV pathogenesis are also being defined. We are also searching for new genes relevant to salivary and craniofacial development and are collaborating with GTTB, NIDCR to develop an artificial salivary gland. These studies should help to clarify mechanisms of pathogenesis and repair, and identify opportunities for prevention and therapeutic intervention in craniofacial congenital defects, cancer, HIV disease, and other disorders.